cDC1 coordinate innate and adaptive responses in the omentum required for T cell priming and memory.

Christian, David A.; Adams II, Thomas A.; Shallberg, Lindsey A.; Phan, Anthony T.; Smith, Tony E.; Abraha, Mosana; Perry, Joseph; Ruthel, Gordon; Clark, Joseph T.; Pritchard, Gretchen Harms; Aronson, Lillian R.; Gossa, Selamawit; McGavern, Dorian B.; Kedl, Ross M.; Hunter, Christopher A.

In the peritoneal cavity, the omentum contains fat-associated lymphoid clusters (FALCs) whose role in response to infection is poorly understood. After intraperitoneal immunization with Toxoplasma gondii, conventional type 1 dendritic cells (cDC1s) were critical to induce innate sources of IFN-γ and cellular changes in the FALCs. Unexpectedly, infected peritoneal macrophages that migrated into the FALCs primed CD8 T cells. Although T cell priming was cDC1 independent, these DCs were required for maximal CD8 T cell expansion. An agent-based computational model and experimental data highlighted that cDC1s affected the magnitude of the proliferative burst and promoted CD8 T cell expression of nutrient uptake receptors and cell survival. Thus, although FALCs lack the organization of secondary lymphoid organs, cDC1s resident in this tissue coordinate innate responses to microbial challenge and provide secondary signals required for T cell expansion and memory formation. Inducing omental immunity: Particulate antigens encountered in the peritoneal cavity are deposited in the omentum next to fat-associated lymphoid clusters (FALCs), a form of organized lymphoid tissue that lacks several structural features usually present in lymph nodes. Using a mouse model of intraperitoneal immunization with a nonreplicating Toxoplasma gondii vaccine strain, Christian et al. explored the role of myeloid cell subsets in enabling initiation of CD8 cell responses within omental FALCs. Whereas presentation of antigen by macrophages was sufficient to prime CD8 T cells, T cell expansion and memory formation also required supportive signals from conventional type 1 dendritic cells (cDC1s). These findings highlight the capacity of cDC1s to provide signals beyond antigen presentation that are critical to efficient induction of adaptive immunity in the omentum.

IMMUNOLOGIC memory; OMENTUM; LYMPHOID tissue; PERITONEUM; ANTIGEN presentation; IMPLICIT memory

Science Immunology, 2022, Vol 7, Issue 75, p1

2470-9468

Academic Journal

10.1126/sciimmunol.abq7432